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Method for preparing cefmetazole sodium

A technology of cefmetazole sodium and cefmetazole acid, which is applied in the field of preparation of cephalosporins, can solve the problems of low yield and product purity, many impurities, deep color, etc., and achieve low cost and environment-friendly effects

Active Publication Date: 2010-07-28
哈药集团股份有限公司 +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Due to the use of sodium hydroxide with too strong alkalinity in this method, there are too many impurities, the content is low, and the color is dark, so the synthesis result of the product is not ideal
[0007] At present, domestic preparation manufacturers mainly rely on imported raw materials to obtain cefmetazole sodium by packaging. There are also some manufacturers in China that produce this product, but the yield and product purity are relatively low. Therefore, research and development of new synthetic methods for this product The method and route have certain social and economic benefits

Method used

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  • Method for preparing cefmetazole sodium
  • Method for preparing cefmetazole sodium
  • Method for preparing cefmetazole sodium

Examples

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Effect test

Embodiment 1

[0043] (1) Preparation of side chain (cyanomethylthioglycolic acid)

[0044] 100ml of water, cooled to 10±2°C, added 20g of sodium hydroxide until completely dissolved, then added 20g of thioglycolic acid, stirred for 10 minutes, added 15g of chloroacetonitrile, reacted for 1 hour; cooled to 10±2°C, added 16.2 g of sodium chloride kg, stir to dissolve, add 90ml of ethyl acetate, dropwise add 36% hydrochloric acid to adjust the pH to 3.5, stir for 10 minutes, stand still and separate the phases, discard the water phase, concentrate the solvent phase to 25-30ml, cool to 0°C-5°C for later use;

[0045] (2) preparation of cefmetazole benzyl axetil

[0046] a: 80ml of dichloromethane, add 50g of phosphorus pentachloride, keep stirring at 10±2°C for 15 minutes, add 12.5ml of side chain (cyanomethylthioglycolic acid) into the solution, timed stirring for 1 hour, set aside;

[0047] b: Add 1000ml of dichloromethane, add 15g of 7-MAC, cool down to -100°C~-10°C, add 5g of organic base,...

Embodiment 2

[0055] (1) Preparation of side chain (cyanomethylthioglycolic acid)

[0056] 100ml of water, cooled to 10±2°C, added 25g of sodium hydroxide until completely dissolved, added 35g of mercaptoacetic acid, stirred for 10 minutes, added 25g of chloroacetonitrile, reacted for 1 hour; cooled to 10±2°C, added 16.2 g of sodium chloride kg, stir to dissolve, add 100ml of ethyl acetate, add dropwise 36% hydrochloric acid to adjust the pH to 3.5, stir for 10 minutes, stand still and separate the phases, discard the water phase, concentrate the solvent phase to 25-30ml, cool to 0°C-5°C for later use;

[0057] (2) preparation of cefmetazole benzyl axetil

[0058] Add 100ml of dichloromethane, add 65g of phosphorus pentachloride, keep stirring at 10±2°C for 15 minutes, add 13ml of side chain (cyanomethylthioglycolic acid) into the solution, and stir for 1 hour to obtain a side chain solution, which is set aside;

[0059] Add 1000ml of dichloromethane, add 18g of 7-MAC, cool down to -100°C~...

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Abstract

The invention relates to a method for preparing cefmetazole sodium, which comprises the following steps: (1) dissolving sodium hydroxide in water, adding mercaptoacetic acid and chloroacetonitrile into the mixture to perform the reaction, then adding sodium chloride and ethyl acetate into the reaction solution, stirring and dissolving the mixture, standing to separate phases and reserving a solvent phase for later use; (2) dissolving 7-MAC in methylene dichloride, adding organic base and side-chain solution into the mixture, stirring the mixed solution to perform the reaction to carry out phase separation, removing a water phase and carrying out secondary phase separation on the solvent phase to obtain cefmetazole benzyl ester; (3) dissolving ferric trichloride in aether, adding methylene dichloride in the mixture, dropwise adding the obtained product into cefmetazole acid to perform the reaction for 0.5 to 1 hour, then carrying out phase separation, removing the water phase, carrying out back extraction of alkali liquor on the solvent phase, then reserving the water phase, adding seed crystals, stirring the product and carrying out crystallization to obtain cefmetazole acid; and (4) dissolving the cefmetazole acid in alkali water and freezing out the mixture to obtain cefmetazole sodium. The preparation method of the invention has the advantages of 58 to 62 percent of yield, low cost, environment-friendly property, 92 percent of product purity, suitability for industrial production and the like.

Description

technical field [0001] The invention belongs to the field of preparation of cephalosporin compounds in the pharmaceutical synthesis technology, and in particular relates to a preparation method of cefmetazole sodium. Background technique [0002] Cefmetazole sodium, its English name is Cefmetazole Sudium, its chemical name is: (6R, 7S)-7-[2-[(cyanomethyl)thio]acetamido]-7-methoxy-3-[ [(1-Methyl-1H-tetrazol-5-yl)thio]methyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2 -Carboxylic acid sodium salt, molecular formula: C 15 h 16 N 7 NaO 5 S 3 , molecular weight: 493.52, structural formula: [0003] [0004] Cefmetazole sodium is a second-generation cephalosporin, which has good stability to broad-spectrum β-lactamase produced by negative bacilli, such as Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Shigella, Salmonella Bacteria and other negative bacilli have good sensitivity to this product. Staphylococcus aureus, group A hemolytic streptococcus, and ca...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D501/57C07D501/04
Inventor 马杰赵玉新王喜军韩东胜黄宇红崔节泉牟春福刘晓艳余威杨洁丁善磊梁轶群李秀艳柳丽新
Owner 哈药集团股份有限公司
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